scholarly journals Platelet Distribution Width Is Associated with P-Selectin Dependent Platelet Function: Results from the Moli-Family Cohort Study

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2737
Author(s):  
Benedetta Izzi ◽  
Alessandro Gialluisi ◽  
Francesco Gianfagna ◽  
Sabatino Orlandi ◽  
Amalia De Curtis ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Platelet Function ◽  
Ex Vivo ◽  
Venous Blood ◽  
Random Effect ◽  
Platelet Distribution Width ◽  
Mixed Effect ◽  
Distribution Width ◽  
Inflammatory Conditions

Defined as an index of platelet size heterogeneity, the platelet distribution width (PDW) is still a poorly characterized marker of platelet function in (sub)clinical disease. We presently validated PDW as a marker of P-selectin dependent platelet activation in the Moli-family cohort. Platelet-bound P-selectin and platelet/leukocyte mixed aggregates were measured by flow cytometry in freshly collected venous blood, both before and after in vitro platelet activation, and coagulation time was assessed in unstimulated and LPS- or TNFα-stimulated whole blood. Closure Times (CT) were measured in a Platelet Function Analyzer (PFA)-100. Multivariable linear mixed effect regression models (with age, sex and platelet count as fixed and family structure as random effect) revealed PDW to be negatively associated with platelet P-selectin, platelet/leukocyte aggregates and von Willebrand factor (VWF), and positively with PFA-100 CT, and LPS- and TNF-α-stimulated coagulation times. With the exception of VWF, all relationships were sex-independent. In contrast, no association was found between mean platelet volume (MPV) and these variables. PDW seems a simple, useful marker of ex vivo and in vitro P-selectin dependent platelet activation. Investigations of larger cohorts will define the usefulness of PDW as a risk predictor of thrombo-inflammatory conditions where activated platelets play a contributing role.

scholarly journals The role of polyphenolic compounds in the diet as inhibitors of platelet function

2003 ◽  
Vol 62 (2) ◽  
pp. 469-478 ◽  
Author(s):  
Gary P. Hubbard ◽  
Siegfried Wolffram ◽  
Julie A. Lovegrove ◽  
Jonathan M. Gibbins
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Platelet Function ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
Polyphenolic Compounds ◽  
Dietary Fats

Platelets play a substantial role in cardiovascular disease, and for many years there has been a search for dietary components that are able to inhibit platelet function and therefore decrease the risk of cardiovascular disease. Platelets can be inhibited by alcohol, dietary fats and some antioxidants, including a group of compounds, the polyphenols, found in fruits and vegetables. A number of these compounds have been shown to inhibit platelet function both in vitro and in vivo. In the present study the effects of the hydroxycinnamates and the flavonoid quercetin on platelet activation and cell signalling in vitro were investigated. The hydroxycinnamates inhibited platelet function, although not at levels that can be achieved in human plasma by dietary intervention. However, quercetin inhibited platelet aggregation at levels lower than those previously reported. Quercetin was also found to inhibit intracellular Ca mobilisation and whole-cell tyrosine protein phosphorylation in platelets, which are both processes essential for platelet activation. The effect of polyphenols on platelet aggregation in vivo was also investigated. Twenty subjects followed a low-polyphenol diet for 3 d before and also during supplementation. All subjects were supplemented with a polyphenol-rich meal every lunchtime for 5 d. Platelet aggregation and plasma flavonols were measured at baseline and after 5 d of dietary supplementation. Total plasma flavonoids increased significantly after the dietary intervention period (P=0·001). However, no significant changes in ex vivo platelet aggregation were observed. Further investigation of the effects of individual polyphenolic compounds on platelet function, both in vitro and in vivo, is required in order to elucidate their role in the relationship between diet and the risk of cardiovascular disease.

Inhibition of human platelet function in vitro and ex vivo by acetaminophen

1989 ◽  
Vol 53 (6) ◽  
pp. 603-613 ◽  
Author(s):  
Bruce Lages ◽  
Harvey J. Weiss
Keyword(s):  
Platelet Function ◽  
Human Platelet ◽  
Ex Vivo

Comparison of the effect of coagulation and platelet function impairments on various mouse bleeding models

2014 ◽  
Vol 112 (08) ◽  
pp. 412-418 ◽  
Author(s):  
Nima Vaezzadeh ◽  
Ran Ni ◽  
Paul Y. Kim ◽  
Jeffrey I. Weitz ◽  
Peter L. Gross
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Saphenous Vein ◽  
Ex Vivo ◽  
Arterial Injury ◽  
Inhibitory Antibody ◽  
Study Objective ◽  
Tail Tip

SummaryHaemostatic impairments are studied in vivo using one of several murine bleeding models. However it is not known whether these models are equally appropriate for assessing coagulation or platelet function defects. It was our study objective to assess the performance of arterial, venous and combined arterial and venous murine bleeding models towards impaired coagulation or platelet function. Unfractionated heparin (UFH) or αIIbβ3 inhibitory antibody (Leo.H4) were administered to mice, and their effects on bleeding in saphenous vein, artery, and tail tip transection models were quantified and correlated with their effects on plasma clotting and ADP-induced platelet aggregation, respectively. All models exhibited similar sensitivity with UFH (EC50 dose = 0.19, 0.13 and 0.07 U/g, respectively) (95% CI = 0.14 – 0.27, 0.08 – 0.20, and 0.03 – 0.16 U/g, respectively). Maximal inhibition of ex vivo plasma clotting could be achieved with UFH doses as low as 0.03 U/g. In contrast, the saphenous vein bleeding model was less sensitive to αIIbβ3 inhibition (EC50 = 6.9 µg/ml) than tail transection or saphenous artery bleeding models (EC50 = 0.12 and 0.37 µg/ml, respectively) (95% CI = 2.4 – 20, 0.05 – 0.33, and 0.06 – 2.2 µg/ml, respectively). The EC50 of Leo.H4 for ADP-induced platelet aggregation in vitro (8.0 µg/ml) was at least 20-fold higher than that of the tail and arterial, but not the venous bleeding model. In conclusion, venous, arterial and tail bleeding models are similarly affected by impaired coagulation, while platelet function defects have a greater influence in models incorporating arterial injury.

scholarly journals Effects of antiplatelet components of tomato extract on platelet function in vitro and ex vivo: a time-course cannulation study in healthy humans

2006 ◽  
Vol 84 (3) ◽  
pp. 570-579 ◽  
Author(s):  
Niamh O’Kennedy ◽  
Lynn Crosbie ◽  
Machteld van Lieshout ◽  
John I Broom ◽  
David J Webb ◽  
...  
Keyword(s):  
Platelet Function ◽  
Time Course ◽  
Ex Vivo ◽  
Healthy Humans ◽  
Tomato Extract

Supplemental Fibrinogen Restores Platelet Inhibitor-Induced Reduction in Thrombus Formation without Altering Platelet Function: An In Vitro Study

2020 ◽  
Vol 120 (11) ◽  
pp. 1548-1556
Author(s):  
Thomas Bärnthaler ◽  
Elisabeth Mahla ◽  
Gabor G. Toth ◽  
Rufina Schuligoi ◽  
Florian Prüller ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Activation ◽  
Platelet Function ◽  
Dual Antiplatelet Therapy ◽  
Thrombus Formation ◽  
In Vitro Study ◽  
Coronary Intervention ◽  
Calcium Flux ◽  
Major Surgery

Abstract Background For patients treated with dual antiplatelet therapy, standardized drug-specific 3-to-7 day cessation is recommended prior to major surgery to reach sufficient platelet function recovery. Here we investigated the hypothesis that supplemental fibrinogen might mitigate the inhibitory effects of antiplatelet therapy. Methods and Results To this end blood from healthy donors was treated in vitro with platelet inhibitors, and in vitro thrombus formation and platelet activation were assessed. Ticagrelor, acetylsalicylic acid, the combination of both, and tirofiban all markedly attenuated the formation of adherent thrombi, when whole blood was perfused through collagen-coated microchannels at physiological shear rates. Addition of fibrinogen restored in vitro thrombus formation in the presence of antiplatelet drugs and heparin. However, platelet activation, as investigated in assays of P-selectin expression and calcium flux, was not altered by fibrinogen supplementation. Most importantly, fibrinogen was able to restore in vitro thrombogenesis in patients on maintenance dual antiplatelet therapy after percutaneous coronary intervention. Conclusion Thus, our in vitro data support the notion that supplementation of fibrinogen influences the perioperative hemostasis in patients undergoing surgery during antiplatelet therapy by promoting thrombogenesis without significantly interfering with platelet activation.

The Effect of Sulphinpyrazone and Its Metabolites on Platelet Function in vitro and ex vivo

1981 ◽  
Vol 10 (3) ◽  
pp. 165-175
Author(s):  
Graham F. Pay ◽  
Robert B. Wallis ◽  
Daniela Zelaschi
Keyword(s):  
Platelet Function ◽  
Ex Vivo

scholarly journals Hemoperfusion leads to impairment in hemostasis and coagulation process in patients with acute pesticide intoxication

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Samel Park ◽  
Md-Imtiazul Islam ◽  
Ji-Hun Jeong ◽  
Nam-Jun Cho ◽  
Ho-yeon Song ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Thrombin Generation ◽  
Degradation Products ◽  
Treatment Modalities ◽  
Platelet Surface ◽  
Distribution Width ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Significant Change

Abstract Hemoperfusion (HP) is one of the important treatment modalities in extracorporeal therapy for patients with acute intoxication. Its use has declined during the past 20 years despite its efficacy, because of its side effects, especially an increased risk of bleeding. Mechanisms of hemostasis impairment have not been clearly elucidated and studies demonstrating the mechanism are lacking. It is not clear which step of the hemostatic process is impaired during HP, and whether it leads to an increased risk of bleeding. We performed both in vivo and in vitro studies to elucidate the mechanism of impairment in the hemostatic process. In patients with acute pesticide intoxication who underwent HP, the platelet count decreased rapidly during the first 30 minutes from 242.4 ± 57.7 × 103/μL to 184.8 ± 49.6 × 103/μL, then gradually decreased even lower to 145.4 ± 61.2 × 103/μL over time (p < 0.001). As markers of platelet activation, platelet distribution width increased continuously during HP from 41.98 ± 9.28% to 47.69 ± 11.18% (p < 0.05), however, mean platelet volume did not show significant change. In scanning electron microscopy, activated platelets adhered to modified charcoal were observed, and delayed closure time after HP in PFA-100 test suggested platelet dysfunction occurred during HP. To confirm these conflicting results, changes of glycoprotein expression on the platelet surface were evaluated when platelets were exposed to modified charcoal in vitro. Platelet expression of CD61, fibrinogen receptor, significantly decreased from 95.2 ± 0.9% to 73.9 ± 1.6%, while those expressing CD42b, von Willebrand factor receptor, did not show significant change. However, platelet expression of CD49b, collagen receptor, significantly increased from 24.6 ± 0.7% to 51.9 ± 2.3%. Thrombin-antithrombin complex, a marker for thrombin generation, appeared to decrease, however, it was not statistically significant. Fibrin degradation products and d-dimers, markers for fibrinolysis, increased significantly during HP. Taken together, our data suggests that hemoperfusion leads to impairment of platelet aggregation with incomplete platelet activation, which was associated with reduced thrombin generation, accompanied by increased fibrinolysis.

scholarly journals Central retinal vein occlusion associated with platelet activation

2019 ◽  
Vol 11 ◽  
pp. 251584141986484 ◽  
Author(s):  
Mehmet Citirik
Keyword(s):  
Retinal Vein Occlusion ◽  
Platelet Activation ◽  
Central Retinal Vein Occlusion ◽  
Mean Platelet Volume ◽  
Control Group ◽  
Platelet Distribution Width ◽  
Platelet Volume ◽  
Distribution Width ◽  
Vein Occlusion ◽  
Central Retinal Vein

Purpose:The aim of this article is to determine and compare the platelet activation by three main platelet activation parameters: mean platelet volume, platelet distribution width, and plateletcrit in patients with central retinal vein occlusion and control subjects.Methods:This study included 30 patients with nonischemic central retinal vein occlusion and 30 control subjects. The levels of mean platelet volume, platelet distribution width, and plateletcrit were measured in all groups.Results:The mean serum level of mean platelet volume was 10.01 ± 0.89 fl in central retinal vein occlusion group and 8.74 ± 1.45 fl in control group. The mean serum level of platelet distribution width was 14.31 ± 1.49% and 11.65 ± 1.81% in central retinal vein occlusion group and control group, respectively. Mean serum plateletcrit value was 0.27 ± 0.07% in central retinal vein occlusion group and 0.23 ± 0.07% in control group. Mean platelet volume, platelet distribution width, and plateletcrit levels were significantly higher in central retinal vein occlusion patients than controls ( p < 0.05).Conclusion:Subclinical platelet activation reflected by mean platelet volume, platelet distribution width, and plateletcrit may have an impact on the genesis of vessel occlusion in central retinal vein occlusion. The results may be important for the clinical management of patients with central retinal vein occlusion.

Novel 12-LOX Inhibitor ML355 Attenuates Platelet Reactivity and Impairs Thrombus Growth, Stability and Vessel Occlusion In Vivo

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3442-3442 ◽  
Author(s):  
Reheman Adili ◽  
Theodore R Holman ◽  
Michael Holinstat
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Vessel Occlusion ◽  
Growth Stability

Abstract Background: Adequate platelet reactivity is required for platelet adhesion and aggregation at the site of vascular injury to maintain hemostasis. However, excessive platelet reactivity can also lead to the formation of occlusive thrombi, the predominate underlying cause of myocardial infarction and stroke. While current anti-platelet treatments limit platelet function, they often result in an increased risk of bleeding. 12-lipoxygenase (12-LOX), an oxygenase highly expressed in the platelet, has been demonstrated by our lab and others to regulate PAR4 and GPVI-mediated platelet reactivity suggesting a role of 12-LOX in regulation of vivo thrombosis. However, the ability to pharmacologically target 12-LOX in vivo has not been established to date. Aims: To determine how 12-LOX regulates thrombus formation in vivo and whether platelet 12-LOX is an effective target for anti-platelet therapeutics, wild-type (WT) or 12-LOX deficient (12-LOX-/-) mice were treated with or without the 12-LOX inhibitor, ML355, and were assessed for inhibitory effects on platelet activation in vitro, ex-vivo and in vivo. Methods: The effect of the novel 12-LOX inhibitor ML355 on human platelet function was assessed in vitro by platelet aggregometry, ex vivo by perfusion chamber. In vivo thrombus formation and vessel occlusion in small and large vessels were studied in 12-LOX-/-, WT mice and mice treated with ML355 using intravital microscopy using the FeCl3 injury models. Results: Using in vitro platelet aggregation assays, ML355 dose dependently inhibited thrombin, PAR1-AP, and PAR4-AP-induced aggregation in washed human platelets. Interestingly, the negative regulatory effects of ML355 inhibition of 12-LOX can be overcome by high concentration of thrombin. Additionally, ML355 was able to attenuate ADP-induced platelet aggregation both in platelet-rich-plasma and whole blood. In ex vivo flow chamber assays, platelet adhesion and thrombus formation on collagen-coated surfaces at high shear was attenuated in both mouse and human whole blood after incubation with ML355. Further, platelet aggregation and thrombus growth in 12-LOX-/- mice was impaired in FeCl3-induced mesenteric or carotid artery thrombosis models. Thrombi in 12-LOX-/- mice were unstable and frequently form emboli, which resulted in impaired vessel occlusion or reopening. Additionally, thrombus formation and vessel occlusion was impaired in ML355 treated WT mice. Conclusions: The highly selective 12-LOX inhibitor ML355 inhibits platelets aggregation induced by various platelet agonists and ML355 inhibition of platelet function is not agonist specific. Platelet function at high shear in ex vivo conditions in both mice and human was attenuated in the presence of ML355. Thrombus growth, stability, and vessel occlusion was impaired in mice deficient for 12-LOX. Finally, the highly selective 12-LOX inhibitor ML355 attenuates thrombus formation and prevents vessel occlusion in vivo. Our data strongly indicates 12- LOX is an important determinant of platelet reactivity and inhibition of platelet 12-LOX may represent a new target for anti-platelet therapeutics. Disclosures No relevant conflicts of interest to declare.

scholarly journals In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation

Blood ◽  
2012 ◽  
Vol 119 (17) ◽  
pp. 4066-4072 ◽  
Author(s):  
Bethan Psaila ◽  
James B. Bussel ◽  
Matthew D. Linden ◽  
Bracken Babula ◽  
Youfu Li ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Platelet Function ◽  
Whole Blood ◽  
Immune Thrombocytopenia ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
High Dose ◽  
Platelet Surface

Abstract The effects of eltrombopag, a thrombopoietin-receptor agonist, on platelet function in immune thrombocytopenia (ITP) are not fully characterized. This study used whole blood flow cytometry to examine platelet function in 20 patients receiving eltrombopag treatment at days 0, 7, and 28. Platelet surface expression of activated GPIIb/IIIa, P-selectin, and GPIb was measured with and without low and high adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) concentrations. Before eltrombopag treatment with no ex vivo agonist, platelet activation was higher in ITP patients than controls. Platelet GPIb and activated GPIIb/IIIa expression without added agonist was unchanged following eltrombopag treatment, whereas a slight increase in P-selectin was observed. Expression of P-selectin and activated GPIIb/IIIa in response to high-dose ADP was lower during eltrombopag treatment than at baseline. Eltrombopag led to a slight increase in platelet reactivity to TRAP only in responders to eltrombopag but not to levels above those in controls; whole blood experiments demonstrated that this increase was probably because of higher platelet counts rather than higher platelet reactivity. In conclusion, although thrombocytopenic ITP patients have higher baseline platelet activation than controls, eltrombopag did not cause platelet activation or hyper-reactivity, irrespective of whether the platelet count increased.

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